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PubMed1995

Nerve-muscle sandwich grafts: the importance of Schwann cells in peripheral nerve regeneration through muscle basal lamina conduits.

An interposed segment of nerve was used to enhance the distance over which freeze-thawed muscle autografts will support effective peripheral nerve regeneration. Gaps were created in the sciatic nerves of adult Lewis rats. Regeneration through 1 and 1.5 cm freeze-thawed muscle grafts was compared to regeneration through nerve-muscle sandwich grafts in which muscle grafts of equivalent length were divided and a 2 mm segment of the distal nerve sutured between the two halves of the muscle, providing an intermediate depot of Schwann cells. Electrophysiological and morphological evaluation was carried out 40 weeks after operation. Despite lengthening the graft, and having four anastomoses instead of two, this manoeuvre enhanced nerve regeneration over each gap studied and for the 1.5 cm gaps compared favourably with perfect match nerve autografts. In addition, a number of grafts were examined at 7 and 14 days by S100 immunohistochemistry. Schwann cell migration was seen to proceed both proximally and distally from the intermediate segment at a rate similar to that from the distal stump. It is concluded that sandwich grafts may prove to be effective alternatives to cutaneous nerve grafts for peripheral nerve reconstruction.

Analysis of Variance↗
PubMed1998

Regulation of semaphorin III/collapsin-1 gene expression during peripheral nerve regeneration.

The competence of neurons to regenerate depends on their ability to initiate a program of gene expression supporting growth and on the growth-permissive properties of glial cells in the distal stump of the injured nerve. Most studies on intrinsic molecular mechanisms governing peripheral nerve regeneration have focussed on the lesion-induced expression of proteins promoting growth cone motility, neurite extension, and adhesion. However, little is known about the expression of intrinsic chemorepulsive proteins and their receptors, after peripheral nerve injury and during nerve regeneration. Here we report the effect of peripheral nerve injury on the expression of the genes encoding sema III/coll-1 and its receptor neuropilin-1, which are known to be expressed in adult sensory and/or motor neurons. We have shown that peripheral nerve crush or transection results in a decline in sema III/coll-1 mRNA expression in injured spinal and facial motor neurons. This decline was paralleled by an induction in the expression of the growth-associated protein B-50/GAP-43. As sema III/coll-1 returned to normal levels following nerve crush, B-50/GAP-43 returned to precrush levels. Thus, the decline in sema III/coll-1 mRNA coincided with sensory and motor neuron regeneration. A sustained decline in sema III/coll-1 mRNA expression was found when regeneration was blocked by nerve transection and ligation. No changes were observed in neuropilin-1 mRNA levels after injury to sensory and motor neurons, suggesting that regenerating peripheral neurons continue to be sensitive to sema III/coll-1. Therefore we propose that a decreased expression of sema III/coll-1, one of the major ligands for neuropilin-1, during peripheral nerve regeneration is an important molecular event that is part of the adaptive response related to the success of regenerative neurite outgrowth occurring following peripheral nerve injury.

Animals↗
PubMedDate not supplied

Pathomechanics of peripheral nerve loading. Evidence in carpal tunnel syndrome.

Peripheral nerve injury is a common occurrence, with carpal tunnel syndrome (CTS) receiving the most attention. Nerve dysfunction associated with compression syndromes results from an interruption or localized interference of microvascular function due to structural changes in the nerves or surrounding tissues. This article reviews the physiologic, pathophysiologic, and histologic effects of compressing peripheral nerves in animal models, and then examines the evidence for similar processes in humans using CTS as a model.

Animals↗
PubMed2005

Technology insight: visualizing peripheral nerve injury using MRI.

Currently, the evaluation of peripheral nerve disorders depends on clinical examination, supplemented by electrophysiological studies. These approaches provide general information on the distribution and classification of nerve lesions-for example, axonal versus demyelinative-but nerve biopsies are still required to obtain morphological and pathophysiological details. In this article, we review recent progress in the imaging of peripheral nerve injury by magnetic resonance (MR) neurography. Axonal nerve injury leads to Wallerian degeneration, resulting in a hyperintense nerve signal on T2-weighted MR images of the distal nerve segment. This signal is lost following successful regeneration. Concomitant denervation-induced signal alterations in muscles can further help us to determine whether nerve trunks or roots are affected. These signal changes are caused by various combinations of nonspecific tissue alterations, however, and are not related to particular pathoanatomical findings, such as inflammation, demyelination or axonal injury. New experimental MR contrast agents, such as gadofluorine M and superparamagnetic iron oxide particles, allow visualization of the dynamics of peripheral nerve injury and repair. Further clinical development of these MR contrast agents should allow these functional aspects of nerve injury and repair to be assessed in humans, thereby aiding the differential diagnosis of peripheral nerve disorders.

Animals↗
PubMed1993

Preservation of peripheral nerve grafts with Schwann cell culture medium.

Preservation of peripheral nerves may, in the near future, play an important role in reconstructive surgery, especially if recent advances in immunosuppressive therapy are taken into account. Therefore, it has to be investigated whether peripheral nerves can be stored for some time after harvesting without diminishing their regenerative potential. Previous experiments of our group could demonstrate only little benefit of organ storage solution (HTK) or normal saline (NaCl 0.9%) to peripheral nerves when kept at cold ischaemia of 4 degrees C for 32 and 72 hours. In this presentation, we are reporting the results of peripheral nerve storage in Dulbecco's Modified Eagle Medium which has been used for Schwann cell culture. In 30 adult Sprague-Dawley rats, a 2.5 cm segment of the right sciatic nerve was harvested and kept at 4 degrees C for 14, 32, 72, and 120 hours. It was then reimplanted into the donor animal; regeneration quality was assessed clinically, histologically and morphometrically after 6 weeks. Best regeneration results were obtained in the 32 and 72 hour groups; regeneration here was comparable to the normal controls. These results are explained with the positive effect of nerve predegeneration.

Animals↗
PubMed2005

Peripheral nerve block techniques for ambulatory surgery.

Peripheral nerve blocks (PNBs) have an increasingly important role in ambulatory anesthesia and have many characteristics of the ideal outpatient anesthetic: surgical anesthesia, prolonged postoperative analgesia, and facilitated discharge. Critically evaluating the potential benefits and supporting evidence is essential to appropriate technique selection. When PNBs are used for upper extremity procedures, there is consistent opioid sparing and fewer treatment-related side effects when compared with general anesthesia. This has been demonstrated in the immediate perioperative period but has not been extensively investigated after discharge. Lower extremity PNBs are particularly useful for procedures resulting in greater tissue trauma when the benefits of dense analgesia appear to be magnified, as evidenced by less hospital readmission. The majority of current studies do not support the concept that a patient will have difficulty coping with pain when their block resolves at home. Initial investigations of outpatient continuous peripheral nerve blocks demonstrate analgesic potential beyond that obtained with single-injection blocks and offer promise for extending the duration of postoperative analgesia. The encouraging results of these studies will have to be balanced with the resources needed to safely manage catheters at home. Despite supportive data for ambulatory PNBs, most studies have been either case series or relatively small prospective trials, with a narrow focus on analgesia, opioids, and immediate side effects. Ultimately, having larger prospective data with a broader focus on outcome benefits would be more persuasive for anesthesiologists to perform procedures that are still viewed by many as technically challenging.

Ambulatory Surgical Procedures↗
PubMed1999

Peripheral nerve injuries secondary to missiles.

Peripheral nerve injuries secondary to missiles can present some of the most challenging problems faced by hand surgeons. This article reviews the pertinent neural anatomy, injury classifications, and repair techniques. Options in the management of nerve gaps are presented including the use of vascularized nerve grafts. The results are discussed and a treatment algorithm is presented.

Algorithms↗
PubMed2005

[Study on using a new biodegradable conduit to repairing rat's peripheral nerve defect].

OBJECTIVE: Nerve conduit, a new way to repair peripheral nerve, has good prospect. Now, the main obstacle of the conduit's clinical using is the absence of material with both ideal physical property and good biocompatibility. In this study, the PLA is added to chitosan to form a novel material used to make a new nerve conduit. And the rat modal is used to get the data of the nerve conduit made of new material to repair the defect of peripheral nerve in vivo. METHODS: Chitosan-PLA Composite Biodegradable material was used to produce a nerve conduit with depth of 200 um, diameter of 1.5 mm. This new conduit was used to repair the sciatic nerve's defect of 5 mm long. The other two groups as control groups repairs the same defects using silicon conduit or nerve's autograft respectively. 12 weeks after operation, normal assessments were performed including movement of hindlimb, hindlimb's retraction after being pricked by needle and ulcer in claw's palm. Special assessment was performed including histology, ECG, image analysis and weighing of triceps muscle of calf. The data of three groups was statistically analyzed by group t test. RESULTS: As the normal observation showing: after 12 weeks, the regenerating nerve succeeded to path through the gap and dominated the muscle. Special assessment including ECG, image analysis and weighing of triceps muscle of calf showed that the group using Chitosan-PLA Composite conduit had the nervous regeneration better than silicon conduit group both in the nerve's quality and in axon's quantity. And the nervous regeneration of Chitosan-PLA Composite conduit group was as good as that of nervous autograft's group. CONCLUSIONS: Chitosan-PLA Composite Biodegradable conduit could repair the defect of peripheral nerves successfully. It is an ideal material for nerve conduit.

Absorbable Implants↗
PubMed2004

Sonographic characteristics of peripheral nerve sheath tumors.

OBJECTIVE: We have found variability in the sonographic appearance of peripheral nerve sheath tumors. The purpose of this study was to characterize the sonographic appearances of pathologically proven peripheral nerve sheath tumors. CONCLUSION: Peripheral nerve sheath tumors are often hypoechoic with posterior acoustic enhancement and so may simulate a ganglion cyst. The presence of intrinsic blood flow on color Doppler sonography and peripheral nerve continuity suggests the diagnosis of peripheral nerve sheath tumor. Sonography cannot reliably distinguish neurofibromas from schwannomas.

Adolescent↗
PubMed1978

A comparative study of the polypeptides of mammalian peripheral nerve myelin.

Polypeptide components of peripheral nerve myelin prepared from sciatic nerves of mouse, rat, rabbit, cat, guinea pig, monkey, dog and chicken were analyzed using a 20% polyacrylamide slab-gel electrophoresis system. Using this technique, we have demonstrated that there are at least two polypeptides present in the region of P1 protein (mol. wt. 18,000 and 16,000), and two closely moving components in the region of P2 protein (mol. wt. 13,500). A polypeptide (mol. wt. 10,500) is present in significant amounts only in mouse sciatic nerve myelin. Staining with periodic acid-Schiff reagent shows that in addition to P0 protein (mol. wt. 28,000), the major glycoprotein of peripheral nerve myelin, there are several minor glycoprotein components in both the high and low molecular weight regions.

Animals↗
PubMed2000

[Benign solitary tumors of the peripheral nerves].

Solitary tumors of the peripheral nerves are uncommon and found to be benign in 90 p. 100 of the cases. They develop from the elements constituting the nerve and are generally schwannomas (80 p. 100). Other tumors are much more exceptional and exhibit wide histological variability. The diagnosis of a tumor of the peripheral nerve must be envisaged for all cases with tumefaction or pain on the path of a nerve exacerbated at percussion. Magnetic resonance imaging is the preferred exploration technique, particularly useful in case of a deep tumor. Preservation of nerve continuity is the underlying goal of the therapeutic strategy, irrespective of the type of tumor. Extricable tumors are to be distinguished from inextricable tumors. Extricable tumors (schwannomas, intranervous lipomas) displace nerve fiber bundles without penetrating into the bundle itself and can thus be resected without interrupting nerve continuity. Prognosis is excellent if no recurrence or degeneration occurs. In case of persistent symptoms, a new exploration may be required to search for other localized tumor(s) unperceived at the first procedure. Inextricable tumors (solitary neurofibromas, hemangiomas of the Schwann sheath, neurofibrolipomas) infiltrate the structural elements of the nerve fibers making complete excision impossible without altering the nerve fibers. Epineurotomy (associated with an interfascicular biopsy for pathology examination) allows decompression and can often provide symptom relief although moderate paresthesia may persist. Patients must be informed of this possibility prior to surgery. Any recent and rapidly evolving modification in the clinical findings is suggestive of recurrence and should be followed by revision exploration. Malignant degeneration has not been observed in solitary tumors to our knowledge. Our own experience with 51 cases is generally in agreement with reports in the literature.

Adult↗
PubMed1996

Changes in the structural properties of peripheral nerves after transection.

Changes in peripheral nerve structural properties after transection were measured weekly for 5 weeks in the distal stump of the sciatic nerve in 50 Sprague-Dawley rats. Each week after transection, the distal stump of the transected nerve showed increased stiffness when compared to intact nerves. Linear elastic stiffness reached a maximum at weeks 1 and 2 after transection, when the transected nerves were 15% stiffer than the contralateral control sides. Toughness was also increased and reached a maximum at week 4 with a 50% difference between values for experimental and control sides. Overall failure load was between 21% and 27% greater, peaking at week 3. An increase in stiffness of the distal stump would result in increased tension at the suture line, as the nerve gap is overcome when performing a delayed neurorraphy. These data suggest, with respect to structural properties, that an end-to-end repair should be carried out at the time of injury; after only 1 week, significant stiffness in the distal segment of the nerve developed, which should result in an increase in tension at the repair site.

Animals↗
PubMed2003

Peripheral nerve lesions: role of high-resolution US.

The peripheral nerve is demonstrated as a reticular pattern in a transverse section at high-resolution ultrasonography (US). Its echogenicity is between that of tendon and muscle. High-resolution US applied to lesions of peripheral nerves yields impressive results in that the nerve is highly differentiated from surrounding soft tissue. In cases of trauma, high-resolution US can easily differentiate between a rupture of the nerve bundle and fibroblast infiltration that results in traumatic neuroma. In cases of inflammation or compressive syndrome, high-resolution US can easily demonstrate lesion location and cause. In the evaluation of abnormal masses, high-resolution US cannot clearly differentiate neurofibromas from schwannomas but it can clarify the relationship between tumor and neural trunk and help the clinician plan treatment strategies. The authors discuss the success that can be achieved with the application of high-resolution US in the evaluation of peripheral nerve lesions.

Adult↗
PubMed1988

Complement receptors CR1 on human peripheral nerve fibres.

Receptors for C3 and C4 in human peripheral nerve tissue were studied by examining the adherence of complement (C) coated erythrocytes (E) and by using monoclonal antibodies against epitopes on the receptors for C3b (CR1), C3d (CR2) and C3bi (CR3). E (erythrocyte)-bearing C3b or C4b adhered to sections of myelinated peripheral nerves and the binding was inhibited only by anti-CR1 antibodies. By immunofluorescence, anti-CR1 antibodies stained the nerve fibres, whereas anti-CR2 and anti-CR3 antibodies did not. The staining was apparently localized to the Schwann cell membrane. E-bearing C3bi or C3d did not adhere to myelinated or unmyelinated nerves. CR1 are therefore the only C3 receptors expressed in human peripheral nerves. E-bearing C3b or C4b did not adhere to unmyelinated nerves from adults or to nerves from fetuses at a gestational age of approximately 21 weeks, whereas monoclonal anti-CR1 antibodies stained myelinated, unmyelinated and fetal nerves equally well. The results indicate that CR1 in unmyelinated and fetal nerves are either functionally inactive or express a lower affinity for C3b/C4b than CR1 in myelinated nerves. There were no significant differences in the binding of E-bearing C3b or C4b to myelinated peripheral nerves from 50 individuals, indicating that CR1 activity is not distributed phenotypically.

Adult↗
PubMed1999

Regulation of fibronectin alternative splicing during peripheral nerve repair.

Wallerian degeneration following peripheral nerve injury is associated with increased production of fibronectin and other extracellular matrix molecules that are thought to enhance repair. We have shown previously that alternative splicing of the mRNA for fibronectin also changes following sciatic nerve lesions so as to reexpress forms of mRNA seen during embryogenesis. In the present study, we have examined the role of the regenerating axons in the regulation of this splicing. We have compared the patterns of fibronectin mRNA splicing seen in sciatic nerve development with that seen in cut nerves (that do not regenerate), crushed nerves (that regenerate successfully), and Schwann cells cultured in forskolin so as to mimic axonal signals. By using a reverse transcriptase polymerase chain reaction assay to examine all three regions of fibronectin mRNA splicing in a quantitative manner, we found that embryonic patterns of fibronectin mRNA splicing appear rapidly following injury and are not then altered by reestablishment of axons in the nerve. In addition, we found that forskolin has no effect on fibronectin mRNA splicing in cultured cells. We conclude that axonal signals do not regulate the pattern of fibronectin alternative splicing in peripheral nerve repair.

Alternative Splicing↗
PubMed2004

N,N-diethyldithiocarbamate produces copper accumulation, lipid peroxidation, and myelin injury in rat peripheral nerve.

Previous studies have demonstrated the ability of the dithiocarbamate, disulfiram, to produce a peripheral neuropathy in humans and experimental animals and have also provided evidence that N,N-diethyldithiocarbamate (DEDC) is a proximate toxic species of disulfiram. The ability of DEDC to elevate copper levels in the brain suggests that it may also elevate levels of copper in peripheral nerve, possibly leading to oxidative stress and lipid peroxidation from redox cycling of copper. The study presented here investigates the potential of DEDC to promote copper accumulation and lipid peroxidation in peripheral nerve. Rats were administered either DEDC or deionized water by ip osmotic pumps and fed a normal diet or diet containing elevated copper, and the levels of metals, isoprostanes, and the severity of lesions in peripheral nerve and brain were assessed by ICP-AES/AAS, GC/MS, and light microscopy, respectively. Copper was the only metal that demonstrated any significant compound-related elevations relative to controls, and total copper was increased in both brain and peripheral nerve in animals administered DEDC on both diets. In contrast, lesions and elevated F2-isoprostanes were significantly increased only in peripheral nerve for the rats administered DEDC on both diets. Autometallography staining of peripheral nerve was consistent with increased metal content along the myelin sheath, but in brain, focal densities were observed, and a periportal distribution occurred in liver. These data are consistent with the peripheral nervous system being more sensitive to DEDC-mediated demyelination and demonstrate the ability of DEDC to elevate copper levels in peripheral nerve. Additionally lipid peroxidation appears to either be a contributing event in the development of demyelination, possibly through an increase of redox active copper, or a consequence of the myelin injury.

Alcohol Deterrents↗
PubMedDate not supplied

Cardiac autonomic involvement and peripheral nerve function in patients with diabetic neuropathy.

The aim of our study was to investigate the relationship between cardiac autonomic neuropathy and dysfunction of myelinated and unmyelinated nerve fibres in the peripheral nerve. We measured nerve conduction velocities, warmth/cold perception thresholds at the foot dorsum, sympathetic skin response (SSR), and performed the quantitative sudomotor axon reflex test (QSART). Forty-three diabetic patients with distal-symmetric polyneuropathy were included. According to the results of heart rate variation, 20 patients had cardiac autonomic neuropathy (CAN+). Apart from motor nerve conduction velocities, all tests were more often abnormal in CAN+ patients. Warmth thresholds (afferent C-fibres) and reduced compound muscle action potentials (CMAPs) of the tibial and peroneal nerve, indicating axonal damage, were more often abnormal in CAN+. Cold threshold and sural nerve conduction velocity were indicators of involvement of myelinated small and large nerve fibres, but not of the cardiac autonomic system. Ninety-four percent (94%) of patients with absent SSR and 78% of patients with abnormal QSART had CAN+. SSR and QSART may be useful for assessment of autonomic neuropathy in diabetic patients with cardiac arrhythmia where direct measurement of heart rate variability is not possible. In the majority of our patients with CAN+, the vagal-cardiac and the sudomotor-sympathetic systems were involved simultaneously, although two entirely different systems were tested. This may reflect a C-fibre directed selectivity of the pathological process in autonomic diabetic neuropathy. In conclusion our results show that diabetics with and without cardiac autonomic neuropathy have a different profile of involvement of peripheral nerve fibres.

Adult↗
PubMed2003

Transplanted neuronal progenitor cells in a peripheral nerve gap promote nerve repair.

A basic experiment of peripheral nerve regeneration using neuronal progenitor cells embedded in collagen gel was performed in a rat sciatic nerve defect. First, when neuronal progenitor cells derived from the fetal rat hippocampus were cultured in atelocollagen-containing medium, neurospheres positive for anti-nestin antibody were confirmed after 8 days. These cells differentiated into astrocytes positive for anti-glial fibrillary acidic protein (GFAP) antibody, oligodendrocytes positive for anti-galactocerebroside (GalC) antibody and neurons positive for anti-neurofilament 200 (NF200) antibody, and they were capable of extending axons. They also differentiated into Schwann-like supportive cells positive for anti-s100 and anti-p75 antibody. Next, a 15-mm defect was prepared in the sciatic nerve of mature rats, and the nerve was bridged with a silicone tube filled with neuronal progenitor cells (1 x 10(5)) embedded in collagen gel. The transplanted neuronal progenitor cells were labeled in advance with 5-bromo-2-deoxyuridine (BrdU). When the regenerated tissue was examined 6 weeks and 10 weeks after grafting, the number and diameter of myelinated fibers were significantly increased compared with a control tube without neuronal progenitor cells. Action potentials were detected in the regenerated nerve. Also, cells positive for both anti-BrdU antibody and anti-S100 or anti-p75 antibody were observed in the regenerated tissue, and part of the grafted neural stem cells were considered to have differentiated into Schwann cell-like supportive cells. From these results neuronal progenitor cells derived from the fetal rat hippocampus are considered to retain their proliferative and differentiating abilities in collagen gel, and when transplanted to a site of peripheral nerve defect, part of them differentiate into supportive cells and they contributed to promotion of axonal regeneration.

Animals↗